This is an application for a K-23 Mentored Career Development Award entitled "Amyloid PET in AD, FTLD & PPA: Diagnosis, Functional & Structural Correlations." The primary goal of the proposed research is to apply PET imaging with the amyloid-beta (AP) ligand Pittsburgh Compound-B (PIB) towards the differential diagnosis of dementia, while simultaneously studying the relationships between amyloid deposition, clinical presentation, and brain structure and function. Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are two leading causes of dementia with distinct histopathologies. Primary progressive aphasia (PPA) is a clinical syndrome that can be caused by FTLD or (less commonly) AD pathology. PIB is a novel PET tracer that specifically binds Ap amyloid, a pathologic hallmark of AD that is not part of the FTLD spectrum. The specific aims of this study are: (1) To measure the utility of PIB-PET in distinguishing AD and FTLD; (2) To identify clinical features that predict the presence of Ap amyloid in PPA and FTLD, and thereby refine diagnostic criteria; (3) To study the relationships between clinical presentation, regional Ap amyloid deposition and neuronal functional and structural integrity using PIB-PET, FDG-PET, and MRI-based cortical thickness measurements. Overall, the proposal seeks to establish PIB-PET as an important clinical tool for improving diagnostic accuracy in dementia, and an important scientific tool for studying the role of Ap amyloid in the pathogenesis of AD. The applicant's long-term goal is to become an independent translational investigator in dementia with expertise in structural, functional and molecular neuroimaging. The applicant seeks training in: (1) neuroimaging, (2) neuropathology and neurobiology of -disease, (S)-biomarker analysis,. (4.) .biostatistics and. data analysis, (5) cognitive and systems neuroscience, (6) clinical dementia care, (7) presentation, Dublication and grant writing and (8) responsible conduct of research. The training program includes mplementing the proposed research plan, didactic courses and instruction from mentors and consultants. Dementia is a leading cause of age-related morbidity and mortality, and a growing strain on health-care resources. The proposed research studies the potential of a new brain imaging technique to improve diagnostic accuracy in dementia, and to study the biology of Alzheimer's disease. [unreadable] [unreadable] [unreadable]